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bioRxiv · 10.1101/2020.08.28.271429

Combinatorial Intracellular Delivery Screening (CIDS) of Anticancer Drugs

Sola-Barrado, B.·Moreira-Leite, D.·Scarpa, E.·Duro-Castano, A.·Battaglia, G.
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Abstract

Conventional drug solubilisation strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, we propose a screening approach in which poorly water-soluble drugs are entrapped in poly (2-(methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC-PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human paediatric glioma cell model, we demonstrated that PMPC-PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediated endocytosis. Additionally, when delivered in combination, drug-loaded PMPC-PDPA POs triggered both an enhanced drug efficacy and synergy compared to that of a conventional combinatorial screening. Hence, our comprehensive synergy analysis illustrates that our screening methodology, in which PMPC-PDPA POs are used for intracellular co-delivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs.

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Sola-Barrado, B., Moreira-Leite, D., Scarpa, E., Duro-Castano, A., Battaglia, G.. 2020-08-31. Combinatorial Intracellular Delivery Screening (CIDS) of Anticancer Drugs. https://doi.org/10.1101/2020.08.28.271429

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